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Marine Biomedical Research

Marine organisms use chemicals to communicate each other, to defend themselves, and to attack others. These chemicals are promising leads for treatments of human diseases, including cancer and infections by bacteria and fungi. We have been collecting marine invertebrates and microorganism in Japan and Indonesia, and searching for natural compounds that inhibit the ubiquitin-proteasome system or show cytotoxic and antimicrobial activities.

Structures and Biosynthesis of Notoamides

Microorganisms are known to be rich sources of biologically active natural products that contain unique structures. The fungi of the genera Aspergillus and Penicillium are known to produce prenylated indole alkaloids, which are derived from tryptophan, proline, and one or two isoprene units constituted of diverse ring systems. We isolated prenylated indole alkaloids, designated notoamides, from the marine-derived fungus Aspergillus protuberus MF297-2, which we isolated in the Noto Peninsula (Japan) by us. The fungus produces various metabolites with the structurally diverse ring systems. During the study of the biosynthetic pathway of the notoamide-related alkaloids, Prof. Williams group reported that the enantiomers of notoamide B and stephacidin A were isolated from the fungus Aspergillus amoenus (formerly Aspergilus versicolor) NRRL 35600, which was isolated from the mushroom in Hawaii. Further, novel congeners, taichunamides, were isolated from the fungus Aspergilus taichungensis IBT 19404, which was isolated from the soil in Taiwan. The fungus produces diastereomers of prenelated indole alkaloids, which were produced by A. protuberus and A. amoenus. Now the study of the biosynthetic pathway is in progress.